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Noble gas neuroprotection: Xenon and argon protect against hypoxic-ischaemic injury in rat hippocampus in vitro via distinct mechanisms

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Title: Noble gas neuroprotection: Xenon and argon protect against hypoxic-ischaemic injury in rat hippocampus in vitro via distinct mechanisms
Authors: Koziakova, M
Harris, K
Edge, C
Franks, N
White, I
Dickinson, R
Item Type: Journal Article
Abstract: Background Noble gases may provide novel treatments for neurological injuries such as ischaemic and traumatic brain injury. Few studies have evaluated the complete series of noble gases under identical conditions in the same model. Methods We used an in vitro model of hypoxia–ischaemia to evaluate the neuroprotective properties of the series of noble gases, helium, neon, argon, krypton, and xenon. Organotypic hippocampal brain slices from mice were subjected to oxygen-glucose deprivation, and injury was quantified using propidium iodide fluorescence. Results Both xenon and argon were equally effective neuroprotectants, with 0.5 atm of xenon or argon reducing injury by 96% (P<0.0001), whereas helium, neon, and krypton were devoid of any protective effect. Neuroprotection by xenon, but not argon, was reversed by elevated glycine. Conclusions Xenon and argon are equally effective as neuroprotectants against hypoxia–ischaemia in vitro, with both gases preventing injury development. Although xenon's neuroprotective effect may be mediated by inhibition of the N-methyl-d-aspartate receptor at the glycine site, argon acts via a different mechanism. These findings may have important implications for their clinical use as neuroprotectants.
Issue Date: 1-Nov-2019
Date of Acceptance: 19-Jul-2019
URI: http://hdl.handle.net/10044/1/71927
DOI: https://dx.doi.org/10.1016/j.bja.2019.07.010
ISSN: 1471-6771
Publisher: Elsevier
Start Page: 601
End Page: 609
Journal / Book Title: British Journal of Anaesthesia
Volume: 123
Issue: 5
Copyright Statement: ©2019 The Authors. Published by Elsevier Ltd on behalf of British Journal of Anaesthesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: British Journal of Anaesthesia
Westminster Medical School Research Trust
Royal Centre for Defence Medicine
British Journal of Anaesthesia
European Society of Anaesthesiology
Ashford and St Peter's Hospitals NHS Foundation Trust
Medical Research Council (MRC)
Medical Research Council (MRC)
The Gas Safety Trust
Royal Centre for Defence Medicine
Funder's Grant Number: 2009(2) NIAA Grants Round
JRC 1-/11 PHD 001
BJA/RCoA Grants NIAA Round 2
Keywords: acute brain injury
carbon monoxide poisoning
hypoxic–ischaemic encephalopathy
noble gases
out-of-hospital cardiac arrest
1103 Clinical Sciences
Publication Status: Published
Online Publication Date: 2019-08-27
Appears in Collections:Imperial College Business School
Department of Surgery and Cancer
Faculty of Natural Sciences